23 replies to this topic

[Anewlife]

Since using amphetamines years ago I have lacked patience, enjoyment and motivation. I was a heavy user for almost a year and upon ceasing only found fish oil to help.

I have recovered probably 75% since then most in the first two years but I'm no where near 100%, in fact I think after the first two years it's been a very gradual decline in my level of functioning, like instead of doing 3 things in a day I will do only one spending too much time at home.

Right now sertraline helps also and I continue to take fish oil as well as do numerous mindfulness exercises but I mostly lack motivation and enjoyment which really sucks.
Having protein at every meal as well as drinking vegetable or fruit smoothies helps only minimally.


I don't want to use any research chemicals or nootropics, I'm after more natural and long term healing supplements similar in effect to fish oil.

If anyone has any experience with this problem and has any suggestions I would love to hear them, thanks.

[MichaelTheAnhedonic]

CDP Choline can upregulate dopamine receptors in long term. But I think in ur case best option is healthy life style + boosting NGF and of course time.

[OneScrewLoose]

How wee you before the amphetamines, and do you have ADHD?

[Fenix_]

Uridine, sulbutiamine, and phenylpiracetam all boost the function of dopamine in various ways. Bacopa and ashwagandha are excellent, though I am not sure how they specifically affect catecholamine neurotransmission.

[OneScrewLoose]

How were you*

[Ark]

http://www.longecity...-73#entry721042

[jroseland]

A 2011 University of California study demonstrated that Modafinil repaired damage that methamphetamine addicts had done to their learning ability with prolonged drug usage:

"The findings suggest that modafinil improves learning in MA-dependent participants, possibly by enhancing neural function in regions important for learning and cognitive control."

[Anewlife]

How wee you before the amphetamines, and do you have ADHD?

I used to be more outgoing, spontaneous and clear headed, I used to get over things easily such as having my sports car in a collision, it's happened twice once before drug use once after(different sports car) the second time bothered me.
I sometimes stutter now.
Also I used to be able to stay at a party or club even if I didn't like the music but now I can't stand it, I get bored and slightly frustrated/anxious and end up going home.
I cbf driving long distances, I used to enjoy driving now I opt for my friend to drive.
I furrow my brow sometimes when I talk or when I'm reading, never used to do this.
I used to be bubbly in social situations now it all depends on my mood.
Likely lots of other things I can't think of at the moment.
I think a lot of the symptoms have to do with my mood and ocd.

[OneScrewLoose]

Do you have ADHD? How much amphetamine did you take per day and in what form (Adderall, Adderall XR, Vyvanse, etc...)

[Anewlife]

I don't have adhd I was taking dextroamphetamine street stuff cut only about 2:1 about a gram a week split up on like 2 or 3 days of the week.

[OneScrewLoose]

I don't have adhd I was taking dextroamphetamine street stuff cut only about 2:1 about a gram a week split up on like 2 or 3 days of the week.

What do you mean cut about 2:1? Cut with what?

A gram a week is quite a bit.

[Flex]

There are several threads about Your issue, I´ll post them if I dont forget it.

9-me-beta cabergoline could be very helpful but also anything that increases GDNF, though too much would decrease dopamine(but I guess theres afaik hardly anything available that does this)

so chinese foxglove could increase GDNF

[csrpj]

Two supplements you might want to look into that currently come to mind are uridine (especially combined with CDP choline and omega-3s), and he shou wu (a top longevity herb from Chinese Medicine that comes with a host of benefits, acting as an MAOI-B in a way that also boosts dopamine levels safely and sustainably)

[HappyShoe]

 

A 2011 University of California study demonstrated that Modafinil repaired damage that methamphetamine addicts had done to their learning ability with prolonged drug usage:

"The findings suggest that modafinil improves learning in MA-dependent participants, possibly by enhancing neural function in regions important for learning and cognitive control."

 

 

This says nothing about repair, it just shows that taking a drug that acts on the same areas of the brain acts as a replacement for it. Says nothing about taking modafinil gets you back to normal after abusing methamphetamine once you're completely sober and no longer taking drugs. Taking Adderall/Dexedrine would do the same thing. Again, absolutely no mention of repair.
 

[HappyShoe]

There are several threads about Your issue, I´ll post them if I dont forget it.

9-me-beta cabergoline could be very helpful but also anything that increases GDNF, though too much would decrease dopamine(but I guess theres afaik hardly anything available that does this)

so chinese foxglove could increase GDNF

 

Don't you mean 9-me-beta carboline?

 

Lithium Orotate increases GDNF, so does Royal Jelly(but only fresh frozen, kept refrigerated, and well preserved)

Edited by HappyShoe, 31 May 2015 - 07:43 AM.

[Flex]

Yes I meant 9-me-beta carboline, was a typo.

Didnt know the GDNF properites of Lithium, though You have to take a certain dose of Lithium for some effects, otherwise it wont work.

 

Here are some infos for "Dopamine repair" and their references:

 

Gastrodin -> GDNF

post #9: Catalpol which is one of the main compounds in Rehmannia Glutinosa

Harpagoside do also increase GDNF

http://www.longecity...ds/#entry704493

 

horny goat weed / Icariin for tyrosine hydrooxilase (TH) and

Polygonatum sibiricum for BDNF

http://www.longecity...ir/#entry706213

 

Various stuff:

http://www.longecity...esting-effects/

 

e.g. Vitamin D3

http://www.longecity...plements/page-2

 

THis is also interresting and was allready several times mentioned:

Jiaogulan = Gynostemma pentaphyllum

 

Increases TH, GNDF as well as other effects

http://www.longecity...od/#entry558462

 

http://www.longecity...mortality-herb/

Edited by Flex, 01 June 2015 - 02:42 PM.

[totflare]

Glycine Uptake Inhibitors as Potential Enhancers of Dopaminergic Axon Regeneration

 

We have found that glycine uptake inhibitors that enhance NMDA glutamate receptor activity promote striatal dopaminergic re-innervation in a toxin-based pre-clinical model of Parkinson’s disease. Adult mice received unilateral intrastriatal 6-OHDA injections. Three weeks after the lesion the dorsal striatum was devoid of dopamine neurites. After an additional four weeks, a gradual and partial dopaminergic re-innervation of the dorsal striatum occurred in untreated mice. This re-innervation was enhanced by 30% when mice were treated with a glycine uptake inhibitor beginning three weeks after the lesion. Dopamine release recordings indicated that this recovery was also functional. Thus, glycine uptake inhibitors promote functional dopaminergic sprouting, a finding that we think should be carefully examined as a new avenue for therapy development for Parkinson’s disease.

 

 

I don't know what the difference is between a glycine uptake and a reuptake inhibitor but sarcosine is a glycine reuptake inhibitor.

Edited by synchronizing89, 05 June 2015 - 08:22 AM.

[Doc Psychoillogical]

My goal is to compile as much information as possible, so I may make it easier on me as well as others to find any and all data and information regarding this topic.

Not only to save everyone time from web-surfing, rereading already discovered info and well, from brain farts.

Those times when its impossible to word what you want to look for in google.

For the sake of Searching, I've made the tile very general, for easy direction from any search engine to this site.

 

 

- Also Tagged specifically for Preferred and Popular Stimulants for this topic.

- I will provide the Data, Posts, Information and sites that I have already found.

- I would LOVE to this discussion topic to full of Vitamins, Supplements, Herbs, Prescriptions, OTC, and Food/Drink Personal experiences & Professional data, research, info, studies, interactions and posts.

 

PLEASE  PROVIDE DIFFERENT AND NEW POSTS, DATA, EXPERIENCES AND INFO!!

http://www.longecity...ts/#entry745153

[gamesguru]

A 2011 University of California study demonstrated that Modafinil repaired damage that methamphetamine addicts had done to their learning ability with prolonged drug usage:

"The findings suggest that modafinil improves learning in MA-dependent participants, possibly by enhancing neural function in regions important for learning and cognitive control."

 

This says nothing about repair, it just shows that taking a drug that acts on the same areas of the brain acts as a replacement for it. Says nothing about taking modafinil gets you back to normal after abusing methamphetamine once you're completely sober and no longer taking drugs. Taking Adderall/Dexedrine would do the same thing. Again, absolutely no mention of repair.

 

Antiparkinsonian and neuroprotective effects of modafinil in the MPTP-treated common marmoset
The psychostimulant drug, modafinil, protects rodents against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity, striatal ischemia and partial transection of the nigro-striatal pathway. We now report on the ability of modafinil to reverse motor disability in MPTP-treated common marmosets and to prevent MPTP-induced nigral cell death in this species. In the initial experiments, adult common marmosets were treated with MPTP to produce stable motor deficits. The subsequent administration of modafinil (10, 30 or 100 mg/kg/day, p.o.) produced a dose-dependent reversal of motor disability.

 

Therapeutic effects of Δ9-THC and modafinil in a marmoset Parkinson model.

[HappyShoe]

 

A 2011 University of California study demonstrated that Modafinil repaired damage that methamphetamine addicts had done to their learning ability with prolonged drug usage:

"The findings suggest that modafinil improves learning in MA-dependent participants, possibly by enhancing neural function in regions important for learning and cognitive control."

 

This says nothing about repair, it just shows that taking a drug that acts on the same areas of the brain acts as a replacement for it. Says nothing about taking modafinil gets you back to normal after abusing methamphetamine once you're completely sober and no longer taking drugs. Taking Adderall/Dexedrine would do the same thing. Again, absolutely no mention of repair.

 

Antiparkinsonian and neuroprotective effects of modafinil in the MPTP-treated common marmoset
The psychostimulant drug, modafinil, protects rodents against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity, striatal ischemia and partial transection of the nigro-striatal pathway. We now report on the ability of modafinil to reverse motor disability in MPTP-treated common marmosets and to prevent MPTP-induced nigral cell death in this species. In the initial experiments, adult common marmosets were treated with MPTP to produce stable motor deficits. The subsequent administration of modafinil (10, 30 or 100 mg/kg/day, p.o.) produced a dose-dependent reversal of motor disability.

 

Therapeutic effects of Δ9-THC and modafinil in a marmoset Parkinson model.

 

 

Yea, but again, that's During treatment, and even then, only motor disability, not cognitive dysfunction. If it induced long term positive changes that lasted after cessation of treatment, then and only then would I be convinced/impressed.
Besides, anyone suffering from such a subjective complaint in the first place is likely experiencing a few different things. An important consideration that is often neglected is the HPAT Axis. I suspect that many people who use stimulants long term, who also complain of such issues, likely also self medicate with marijuana to deal with some of the side effects of amphetamine use, which causes unfavorable gene expression with regards to dopamine and other related hormones. In theory, cessation of use, a healthy diet, some specific supplements like Magnesium, EGCG, Omega 3's, in addition to something to balance the HPAT Axis like Tianeptine could be favorable. All that would be pointless if you didn't maintain an excellent sleep schedule, exercise regularly(but not too intensely, with a gradual buildup), as well as avoiding Stress as much as possible. Even then, recovery would likely take a long time even maintaining all that perfectly, and that's just in theory.

Don't get me wrong, I absolutely LOVE the idea that I could take something that made me feel good, acting as a band aid for a cognitive crippling, that also healed the brain/body and restored proper mental function? Would be sold in a heart beat, but until I see precise wording that says that's the case months after no longer taking Modafinil, then it doesn't prove what everyone seems to be thinking; it's just replacing it, not fixing it.

http://www.ncbi.nlm....pubmed/25431526
Oxidative Damage caused by Modafinil, including the Striatum.

Edited by HappyShoe, 28 September 2015 - 01:23 PM.

[gamesguru]

There is also evidence for a neuroprotective effect of modafinil on MPTP-induced nigrostriatal DA neuronal toxicity, even with a delayed administration that renders other DAT inhibitors ineffective (Aguirre et al, 1999; Fuxe et al, 1992).

Modafinil: A Review of Neurochemical Actions and Effects on Cognition

 

 

Modafinil appears to have a very favorable effect on nigrostriatal health, at least in the short-term, perhaps like levo+carbidopa, by elevating DA levels (which would potentially be toxic/oxidative/desensitizing long-term).

There are some concerning studies, examining areas other than the nigrostriatal pathway.

 

Effect of modafinil on learning performance and neocortical long-term potentiation in rats
Modafinil is a novel wake-promoting agent whose effects on cognitive performance have begun to be addressed at both preclinical and clinical level. The present study was designed to investigate in rats the effects of chronic modafinil administration on cognitive performance by evaluating: (i) working and reference memories in an Olton 4×4 maze, and (ii) learning of a complex operant conditioning task in a Skinner box. In addition, the effect of modafinil on the ability of the rat frontal cortex to develop long-term potentiation (LTP) was also studied. Chronic modafinil did not significantly modify working memory errors but decreased long-term memory errors on the Olton 4×4 maze, meaning that the drug may have a favourable profile on performance of visuo-spatial tasks (typically, a hippocampus-dependent task) when chronically administered. On the other hand, chronic modafinil resulted in a marked decrease of successful responses in a complex operant conditioning learning, which means that repeated administration of the drug influences negatively problem-solving abilities when confronting the rat to a sequencing task (typically, a prefrontal cortex-dependent task). In addition, in vivo electrophysiology showed that modafinil resulted in impaired capacity of the rat prefrontal cortex to develop LTP following tetanization. It is concluded that modafinil can improve the performance of spatial tasks that depend almost exclusively on hippocampal functioning, but not the performance in tasks including a temporal factor where the prefrontal cortex plays an important role. The fact that modafinil together with preventing operant conditioning learning was also able to block LTP induction in the prefrontal cortex, suggests that the drug could interfere some critical component required for LTP can be developed, thereby altering neuroplastic capabilities of the prefrontal cortex.

 

with potential for abuse in predisposed/addictive personalities...

Effects of Modafinil on Dopamine and Dopamine Transporters in the Male Human Brain: Clinical Implications
Modafinil, a wake-promoting drug used to treat narcolepsy, is increasingly being used as a cognitive enhancer. Although initially launched as distinct from stimulants that increase extracellular dopamine by targeting dopamine transporters, recent preclinical studies suggest otherwise.
To measure the acute effects of modafinil at doses used therapeutically (200 mg and 400 mg given orally) on extracellular dopamine and on dopamine transporters in the male human brain.
Positron emission tomography with [11C]raclopride (D2/D3 radioligand sensitive to changes in endogenous dopamine) and [11C]cocaine (dopamine transporter radioligand) was used to measure the effects of modafinil on extracellular dopamine and on dopamine transporters in 10 healthy male participants. The study took place over an 8-month period (2007–2008) at Brookhaven National Laboratory.
Primary outcomes were changes in dopamine D2/D3 receptor and dopamine transporter availability (measured by changes in binding potential) after modafinil when compared with after placebo.
Modafinil decreased mean (SD) [11C]raclopride binding potential in caudate (6.1% [6.5%]; 95% confidence interval [CI], 1.5% to 10.8%; P=.02), putamen (6.7% [4.9%]; 95% CI, 3.2% to 10.3%; P=.002), and nucleus accumbens (19.4% [20%]; 95% CI, 5% to 35%; P=.02), reflecting increases in extracellular dopamine. Modafinil also decreased [11C]cocaine binding potential in caudate (53.8% [13.8%]; 95% CI, 43.9% to 63.6%; P<.001), putamen (47.2% [11.4%]; 95% CI, 39.1% to 55.4%; P<.001), and nucleus accumbens (39.3% [10%]; 95% CI, 30% to 49%; P=.001), reflecting occupancy of dopamine transporters.
Conclusions
In this pilot study, modafinil blocked dopamine transporters and increased dopamine in the human brain (including the nucleus accumbens). Because drugs that increase dopamine in the nucleus accumbens have the potential for abuse, and considering the increasing use of modafinil, these results highlight the need for heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations.

Modafinil: Preclinical, Clinical, and Post-Marketing Surveillance—A Review of Abuse Liability Issues
Modafinil is an agent that is frequently used in the treatment of narcolepsy. More recently it has been used in the treatment of a variety of psychiatric, neurological, and medical illnesses. Due to its ability to improve wakefulness, modafinil has been viewed as a stimulant. Based on the potential for modafinil to become widely used in a variety of syndromes and settings, evidence from preclinicalin vitro andin vivo studies, human laboratory studies, and post-marketing experiences examining the potential abuse liability of modafinil were reviewed. Initial evidence suggests that modafinil has limited potential for large-scale abuse.

[normalizing]

anything new, besides talk about modafinil?

 

Glycine Uptake Inhibitors as Potential Enhancers of Dopaminergic Axon Regeneration

 

We have found that glycine uptake inhibitors that enhance NMDA glutamate receptor activity promote striatal dopaminergic re-innervation in a toxin-based pre-clinical model of Parkinson’s disease. Adult mice received unilateral intrastriatal 6-OHDA injections. Three weeks after the lesion the dorsal striatum was devoid of dopamine neurites. After an additional four weeks, a gradual and partial dopaminergic re-innervation of the dorsal striatum occurred in untreated mice. This re-innervation was enhanced by 30% when mice were treated with a glycine uptake inhibitor beginning three weeks after the lesion. Dopamine release recordings indicated that this recovery was also functional. Thus, glycine uptake inhibitors promote functional dopaminergic sprouting, a finding that we think should be carefully examined as a new avenue for therapy development for Parkinson’s disease.

 

 

I don't know what the difference is between a glycine uptake and a reuptake inhibitor but sarcosine is a glycine reuptake inhibitor.

 

 

 

this one i also found interesting. anyone has something to chime in here?

 

[Junk Master]

I know you mentioned no RC's but NSi-189 seems like a good fit.

[normalizing]

whats the mechanism by which nsi-189 works? as far as i know its still research chemical and there is no conclusive mechanism by which it works and that is not a comfortable thing to know if to experiment with it